DESCRIPTION, OVERALL (provided by applicant): We propose a Center of Exellence in Molecular Hematology (CEHM) with the theme of metal metabolism and heme biosynthesis. The CEMH will support the activities of 17 NIH-supported investigators from multiple departments at the University of Utah and five other universities. These investigators focus on iron, copper, and zinc and on the biosynthesis of porphyrins and heme in normal and disease states. Research in metal metabolism emphasizes the genetic and biochemical basis of metals, including homeostasis uptake, transport, and cellular distribution. Genes of interest are studied in yeast, zebrafish, worms, and mouse models. Results from model systems are used to test clinical hypotheses. These studies are facilitated by the availability of large pedigrees with inherited iron overload disorders. Research in porphyria and heme biosynthesis extends from structural studies of porphyrin biosynthetic enzymes to animal models of human porphyrins. Again, large pedigrees with inherited disorders of porphyrin metabolism are available for translational studies. The CEMH will support four Cores that will facilitate research on metals and heme. These Cores include X-Ray Crystallography, Protein Purification, and Metabolomics. We expect the Metabolomics Core to be national reference centers for studies on metals and heme. The CEMH will also support pilot projects directed both at translational research and at identification of genes that affect metal uptake transport and distribution. The pilot projects take advantage of Utah's strengths in genetic analysis, metal physiology, and a large accessible patient population.